Researchers from the Flinders University, Australia and University of Miami have discovered a new protein that can act as a biomarker to track disease progression in people with MND. A paper written under the leadership of Dr Shepheard and Dr Rogers was published today in the research journal ‘Neurology’.
What is p75 and what do we know so far
The biomarker is a protein called p75, which initially
supports the growth of neurones during embryonic development and its levels markedly decrease after birth. Throughout our lives, p75 only reappears in higher levels when the body detects injury of the nervous system, and shows its presence in urine.
The researchers have previously shown that, after birth, mice with a mutation in the SOD1 gene, known to cause MND, had high levels of p75 after about 40 days from the onset of MND. This also coincided with increased levels of p75 in motor neurones found in tissue of people with MND after death.
What was the study about?
Following on from previous findings, samples of urine from 54 people with MND were compared to those from 45 healthy ‘control’ participants and levels of p75 protein were observed. The amount of p75 was significantly higher in people with MND compared to healthy controls; average levels of p75 were 5.6 versus 3.6 ng/mg creatinine, respectively (the levels of p75 were given as proportion of how much was in the urine to make comparisons between different samples easier to do).
As well as measuring p75 levels in each person once, the researchers made repeat measurements over time. Thirty one people with MND were followed up for up to 30 months and the levels of p75 were tracked. Their urine samples showed a stable increase of p75 levels by about 0.19 ng/mg creatinine per month. This means that the further the disease has progressed, the greater amount of p75 was found in the urine.
Why are these findings important?
Discovery of new biomarkers is one of the ultimate goals on our way to treat and beat MND. Knowing that the presence of a certain substance in the body is directly associated with a certain disease gives us an objective biological measure of the disease progression. This is crucial for clinical trials as the effects of new treatments can be measured by comparing the levels of biomarkers. Urinary p75 is an exciting new biomarker that can be used for MND research studies. It will be important to collect data on how levels of p75 change in larger numbers of people with MND over time, a work that is currently ongoing as a part of the CReATe consortium. You can find more information about the consortium on their dedicated webpages.
So far, progression of MND in clinical trials has been monitored by analysing patients’ blood and cerebrospinal fluid (‘cushioning’ fluid encasing the brain) or by observing their symptoms using the ALS-FRS questionnaire. A biomarker measureable in urine is easier to collect, and may mean that people with MND are more likely to take part in a clinical trial.
Note. ng/mg creatinine – measure of concentration of p75 in nanograms for 1 milligram of creatinine (a breakdown molecule present in urine)
Original research paper: Shepheard, S. R., Wuu, J., Cardoso, M, Wiklendt, L., Dinning, P., Chataway, T., Schultz, D., Benatar, M. and Rogers, M. (2017) Urinary p75. A prognostic, disease progression, and pharmacodynamic biomarker in ALS. Neurology, 88.
Are patients being offered the trial drugs all over the World? My husband had MND and we have not been made aware or offered trial drugs fir a chance of a better quality of life ,
Tracey – UK
Dear Tracey,
Thank you for your comment.
We regularly advertise any new treatment trials that are recruiting new participants via our website and we also share any clinical trial updates via our Twitter account (@mndresearch). There is a list of clinical trials that are happening all over the world at www.clinicaltrials.gov where you can find more detailed information about each study.
If you want to find out more about how clinical trials are organised, we recommend to read our dedicated information sheet.
Martina
Can you find how to stop build up of p75
Dear Mark,
Thank you for your comment.
p75 only appears in our urine as a result of injury to neurones. This is because once a neurone is ‘in stress’, a part of p75 sheds from motor neurones and is excreted via urine. We should therefore look at p75 as a ‘neutral’ marker that helps us identify presence of a disease rather than something we want to get rid of.
This is in contrast with TDP-43, which is a protein that accumulates within motor neurones and contribute to their death. While it is also a biomarker as it informs us about the presence of MND, we look at it more as a ‘negative’ biomarker because it has adverse effects to the body.
What about other neurological disorders. Would p75 be present in those diseases too?
Dear Robyn,
Thank you for your comment.
Yes, increases of p75 are observed in various injuries relating to both central (relating to the brain and spinal cord) and peripheral (relating to the peripheries/extremities) nervous system. Previous research mainly worked on p75 increases in Alzheimer’s disease, Parkinson’s disease and optic nerve injury. In their previous paper, Shepheard et al. (2014) stated that the amount of p75 in urine was higher in MND than Parkinson’s disease, which was also higher than in healthy controls.
Martina